Abstract

The interaction of amphiphilic molecules such as lipids and surfactants with the hydrophilic
drug carboplatin was investigated to identify suitable self-assembling components
for a potential gel-based delivery formulation. (1) H-NMR Studies in sodium bis(2-ethylhexyl)
sulfosuccinate (aerosol-OT, AOT)-based reverse micelles show that carboplatin associates
and at least partially penetrates the surfactant interface. Langmuir monolayers formed
by dipalmitoyl(phosphatidyl)choline are penetrated by carboplatin. Carboplatin was
found to also penetrate the more rigid monolayers containing cholesterol. A combined
mixed surfactant gel formulation containing carboplatin and cholesterol for lymphatic
tissue targeting was investigated for the intracavitary treatment of cancer. This
formulation consists of a blend of the surfactants lecithin and AOT (1 : 3 ratio),
an oil phase of isopropyl myristate, and an aqueous component. The phases of the system
were defined within a pseudo-ternary phase diagram. At low oil content, this formulation
produces a gel-like system over a wide range of H(2) O content. The carboplatin release
from the formulation displays a prolonged discharge with a rate three to five times
slower than that of the control. Rheological properties of the formulation exhibit
pseudoplastic behavior. Microemulsion and Langmuir monolayer studies support the interactions
between carboplatin and amphiphilic components used in this formulation. To target
delivery of carboplatin, two formulations containing cholesterol were characterized.
These two formulations with cholesterol showed that, although cholesterol does little
to alter the phases in the pseudo-ternary system or to increase the initial release
of the drug, it contributes significantly to the structure of the formulation under
physiological temperature, as well as increases the rate of steady-state discharge
of carboplatin.